Science and technology studies analyses of emerging forms of treatment often result in the detailed display of complexities and at times lead to explicit critiques of particular healthcare practices. Simultaneously, there seems to be an increasing interest in exploring more experimental engagements by STS researchers in the proactive construction of such practices. In this article, I explore the relevance of experimental interventions in health care practices for both these care practices and for issues of the normativity of STS research. By (...) analyzing my involvement in changes in the practice of hemophilia home treatment, I indicate how this care practice was reconfigured, partly by drawing on STS insights on the issue of compliance. I also claim that experimenting with forms of ‘‘artful contamination’’ allow STS researchers to do normativity in the practices they engage with. Such practices of interventionist STS research may be of value for refiguring debates in which constructivism has been accused of being normatively deficient. This may make interventionist STS research a fruitfully risky business. (shrink)

BackgroundGenetic disorders due to kindred marriages are common medical conditions in Iran; however, the legal aspects of abortion remain controversial. This study was undertaken to determine physicians' opinions regarding the termination of pregnancy for three genetic diseases: thalassemia major, hemophilia, and Down's syndrome.MethodsA questionnaire was administered to selected physicians by stratified random sampling to determine the following: age, gender, knowledge about prenatal diagnosis of diseases in high risk pregnancies, agreement with abortion, recommended gestational age for abortion, and, if opposed (...) to abortion, the reason.ResultsOf 323 physicians, who participated in the study, 91.3(295), 40.6(131), and 78.6%(254) were in agreement and 8.7(28), 59.4(192), and 21.4%(69) were opposed to abortion for thalassemia major, hemophilia, and Down's syndrome, respectively. Among 289 physicians opposed to abortion in respect of each of all three conditions, the following reasons were cited: religion, 18; emotional, 10; quality of care, 23; hope to find a new treatment option in the future, 103; miscellaneous reasons, 6; and a combination of these reasons, 129. Among 680 physicians in agreement with abortion in relation to all of the diseases, 4.6%(31) were agreed with abortion in less than 12 weeks gestation, 79.2%(538) in less than 16 weeks gestation, 5.6%(38) in less than 20 weeks gestation, 2.2%(15) in less than 24 weeks gestation, and 8.4%(58) were agreed with beyond the 24 weeks of gestational age.ConclusionThe majority of physicians were in agreement with abortion for thalassemia major and Down's syndrome because of the overall prognosis, but opposed to abortion for hemophilia. (shrink)

Moore, Gerard Review(s) of: The Billycart, the boxing tent, the battle: Life with haemophilia, by Anne Kearney, (Bloomington IN: Xlibris, 2013) pp.59, ISBN 9781483662893, $36.99.

The rule of rescue describes the moral impulse to save identifiable lives in immediate danger at any expense. Think of the extremes taken to rescue a small child who has fallen down a well, a woman pinned beneath the rubble of an earthquake, or a submarine crew trapped on the ocean floor. No effort is deemed too great. Yet should this same moral instinct to rescue, regardless of cost, be applied in the emergency room, the hospital, or the community clinic? (...) -/- In health care, the desire to save lives at any cost must be reconciled with the reality of resource scarcity. As one example, the estimated cost for prophylactic Factor VIII to treat one patient with hemophilia for one year is $300,000. Costs of this magnitude have been accepted by public and private insurers in the developed world, even though, in principle, these sums could provide greater overall health benefit if allocated to pay for the unmet health care needs of many other patients. Looking forward, however, broad application of the rule of rescue will be increasingly untenable. But the moral instinct will remain: the desire to help those weakest among us, especially when their small numbers allow us to see them as unique individuals. What, then, is the ethical framework that can guide coverage and reimbursement decisions for orphan drugs into the future? (shrink)

Eells and Sober proved in 1983 that screening off is a sufficient condition for the transitivity of probabilistic causality, and in 2003 Shogenji noted that the same goes for probabilistic support. We start this paper by conjecturing that Hans Reichenbach may have been aware of this fact. Then we consider the work of Suppes and Roche, who demonstrated in 1986 and 2012 respectively that screening off can be generalized, while still being sufficient for transitivity. We point out an interesting difference (...) between Reichenbach’s screening off and the generalized version, which we illustrate with an example about haemophilia among the descendants of Queen Victoria. Finally, we embark on a further generalization: we develop a still weaker condition, one that can be made as weak as one wishes. (shrink)

The development of gene therapy has always come with the expectation that it will offer a cure for various disorders, of which hemophilia is a paradigm example. However, although the term is used regularly, it is unclear what exactly is meant with “cure”. Therefore, the aim of this paper is to analyse how the concept of cure is used in practice and evaluate which of the interpretations is most suitable in discussions surrounding gene therapy. We analysed how cure is (...) used in four different medical fields where the concept raises discussion. We show that cure can be used in three different ways: cure as normalization of the body, cure as obtaining a normal life, or cure as a change in identity. We argue that since cure is a practical term, its interpretation should be context-specific and the various uses can exist simultaneously, as long as their use is suitable to the function the notion of cure plays in each of the settings. We end by highlighting three different settings in the domain of hemophilia gene therapy in which the term cure is used and explore the function(s) it serves in each setting. We conclude that in the clinical application of gene therapy, it could be better to abandon the term cure, whereas more modest and specified definitions of cure are required in the context of health resource allocation decisions and decisions on research funding. (shrink)

While ethics and evidence‐based medicine are often viewed as separate domains of inquiry and practice, what we know influences what we can ethically justify doing, and what we see as our moral obligations shapes the way we interpret evidence. The boundaries between the moral and epistemic spheres become particularly blurred when the health of people is at stake and even more so when no “officially” recommended medical intervention is available to help a patient in need. The treatment of major hemorrhages (...) using recombinant factor VIIa (rFVIIa), which was originally approved under orphan drug legislation to treat hemophilia, is a case in point.Following reports in the late 1990s that rFVIIa was success­fully used to stop bleeding in gunshot trauma, there was much excitement about its potential to help patients with uncontrolled bleeding in other clinical settings, leading to wide‐spread off‐label use of the drug. In recent years, new evidence has raised questions about the off‐label use of rFVIIa for severe bleeding. Nonetheless, while some clini­cians are now adamantly opposed to prescribing rFVIIa for massive bleed­ing, many remain determined to continue the practice. This raises the question: why do clinicians have such variable responses to the same body of evidence?We analyzed the debate around off‐label use of rFVIIa and character­ized its main conceptual features and tensions. We did not seek to provide a normative analysis as to whether the evidence supports the case for off‐label prescribing, nor did we try to provide a historical analysis of how attitudes and clinical practice have changed. Rather, we sought to make visible the moral and epistemic values underpinning stakeholders’ opinions and practices. On the basis of our analysis, which is described in this ar­ticle, we suggest that debates such as those surrounding rFVIIa will not be resolved simply by conducting more studies and that, therefore, there is also a need for conceptual and pro­cedural frameworks that more sys­tematically incorporate values into clinical policy‐making. (shrink)

ABSTRACTRelatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer’s most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied with (...) various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations’ health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short‐course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. (shrink)

Is it justified to detect minor genetic aberrations before birth and terminate pregnancies based upon such information? We present the case of a woman who wanted Prenatal Diagnosis to detect whether her female fetus was a Haemophilia mutation carrier. Such carriers are usually healthy.She wished to eradicate the Haemophilia mutation from her family to avoid future generations being affected and to protect her children from having to go through PND themselves. We explore existing practice guidelines, public attitudes and possible objections (...) to providing PND for minor abnormalities. We argue that in a society where couples have considerable autonomy relating to decisions about the fetus at least until viability, the routine restriction of PND for minor genetic abnormalities would be an unjust infringement of individual liberty. (shrink)

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it might be useful to evaluate (...) the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used. (shrink)

Plasma protein therapies are a group of essential medicines extracted from human plasma through processes of industrial scale fractionation. They are used primarily to treat a number of rare, chronic disorders ensuing from inherited or acquired deficiencies of a number of physiologically essential proteins. These disorders include hemophilia A and B, different immunodeficiencies and alpha 1-antitrypsin deficiency. In addition, acute blood loss, burns and sepsis are treated by PPTs. Hence, a population of vulnerable and very sick individuals is dependent (...) on these products. In addition, the continued well-being of large sections of the community, including pregnant women and their children, travelers and workers exposed to infectious risk is also subject to the availability of these therapies. Their manufacture to adequate amounts requires large volumes of human plasma as the starting material of a complex purification process. Mainstream blood transfusion services run primarily by the not-for-profit sector have attempted to provide this plasma through the separation of blood donations, but have failed to provide sufficient amounts to meet the clinical demand. The collection of plasma from donors willing to commit to the process of plasmapheresis, which is not only time consuming but requires a long term, continuing commitment, generates much higher amounts of plasma and has been an activity historically separate from the blood transfusion sector and run by commercial companies. These companies now supply two-thirds of the growing global need for these therapies, while the mainstream government-run blood sector continues to supply a shrinking proportion. The private sector plasmapheresis activity which provides the bulk of treatment products has been compensating the donors in order to recognize the time and effort required. Recent activities have reignited the debate regarding the ethical and medical aspects of such compensation. In this work, we review the landscape; assess the contributions made by the compensated and non-compensated sectors and synthesize the outcomes on the relevant patient communities of perturbing the current paradigm of compensated plasma donation. We conclude that the current era of “Patient Centeredness” in health care demands the continuation and extension of paid plasma donation. (shrink)

In 2017, Americans spent over $3.4 trillion-nearly 18% of gross domestic poduct-on health care. This spending is unevenly distributed: Almost a quarter is spent on the costliest 1% of patients, and almost half on the costliest 5%. Most of these patients soon return to a lower percentile, but many continue to incur health care costs in the top percentiles year after year. This Article focuses on the challenges that persistently expensive patients present for health law and policy, and how fairly (...) dividing their medical costs among payers illuminates fundamental normative choices about the design and reform of health insurance. In doing so, this Article draws on bioethical and health policy analyses of the fair distribution of medical costs, and examines how legal doctrine shapes health systems' options for responding to expensive patients. Part I of this Article discusses two real-world examples of expensive patients and the debate surrounding them, including the case of an Iowa teenager with hemophilia whose treatments cost more than $10 million per year. Part II then examines the normative question of how the costs of treating expensive patients' medical conditions should be shared and identifies three different dimensions of sharing: (1) scope, from narrow (plan members only) to broad (all of society); (2) boundedness, whether there are limits on the costs others can be asked to bear; and (3) progressivity, whether wealthier individuals are asked to bear more costs (similar to progressivity in tax). Part III then considers how health care reform choices could advance or hamper the adoption of broad, bounded, progressive sharing, with a focus on recent state-level reinsurance programs that legal scholarship has not yet analyzed in depth. -/- This Article contributes to the literature on health care reform in three interlocking ways. First, it develops a novel proposal for fairly sharing the cost of expensive patients' care that could usefully inform state- and federal-level policy discussions. Second, it provides a normative, rather than purely political or economic, analysis of existing and proposed options for sharing expensive patients' costs. Third, it bridges the disconnected literature on reinsurance, limit setting, and health care financing, identifying how proposals in these different areas intersect. (shrink)

and heavily influenced by culture, (as opposed to, say, " gene for haemophilia", or "gene for colour blindness", whose effects are entirely Features physical).

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

Catastrophically bad decisions were an all-too-frequent occurrence when it came to managing blood for therapeutic purposes in the first decade of the AIDS epidemic. The victims of those bad decisions were, first and foremost, the persons who received HIV-contaminated blood via their medical treatments. During the 1980s, at least 20,000 patients in the United States contracted HIV infections via "tainted" blood treatments. More than half of the nation's 16,000 hemophilia patients were among that number. Unlike the roughly 12,000 Americans (...) who contracted HIV through a standard whole blood transfusion during that decade, nearly all of these hemophilia patients contracted HIV from a commercially manufactured clotting... (shrink)

Correct interpretation of the data from integral laboratory tests, including Thrombin Generation Test, requires biochemistry-based mathematical models of blood coagulation. The purpose of this study is to describe the experimental TGT data from healthy donors and hemophilia A and B patients. We derive a simplified ODE model and apply it to analyze the TGT data from healthy donors and HA/HB patients with in vitro added tissue factor pathway inhibitor antibody. This model allows the characterization of hemophilia patients in (...) the space of three most important model parameters. The proposed approach may provide a new quantitative tool for the analysis of experimental TGT. Also, it gives a reduced model of coagulation verified against clinical data to be used in future theoretical large-scale modeling of thrombosis in flow. (shrink)

Peter Singer’s recent appointment to Princeton University created considerable controversy, most of it focused on his proposal for active euthanasia of disabled infants. Singer articulates utilitarian ideas that often appear in public discussions of euthanasia. Drawing on Pope John Paul II’s work on ethics and suffering, I argue that Singer’s utilitarian theory of value is impoverished. After introducing the Pope’s ethic based on the imago dei, I discuss love as self-gift. I show how this concept supports a theory of value (...) in which spiritual goods are preeminent over material goods. I then describe how suffering reveals spiritual goods, discussing how participation in Christ’s suffering can alter our perception of value. I also consider how communal responses to suffering provide opportunities for self-giving. Third, I consider Singer’s proposal for killing infants with hemophilia, arguing that it arbitrarily ignores spiritual goods. I then discuss proposals to kill anencephalic infants, discussing how parental response to their suffering can demonstrate an extraordinary love in seemingly hopeless circumstances. I conclude by calling for a more sustained social response to euthanasia initiatives. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The National Commission on AIDSDonald S. Goldman (bio) and Jeff Stryker (bio)A decade after the first cases were recognized in the United States, AIDS continues to vex policymakers and fascinate the public. It has been said that AIDS acts as a prism, refracting a spectrum of controversial topics. For bioethicists, these topics include: equity in the allocation of resources for treatment and research; forgoing life-sustaining care and proxy decision (...) making; informed consent in the context of HIV testing and screening; the ethical duties of health care workers to provide care for persons with HIV disease; and competing obligations of health care professionals to patients and to third parties who may be put at risk.The Role of CommissionsIf AIDS is the quintessential case study for bioethicists, it is a potential quagmire for politicians. The association of HIV disease with drug use and sexual behavior makes it a topic that all but the most courageous (or the most homophobic) politicians shy away from. A frequent political response is to form a commission.Alexander Capron, who was executive director of the President's Commission for the Study of Ethical Problems in Medicine, has described some roles commissions play: a watchdog, overseeing the work of particular government agencies; a crucible, providing a means for "publicly hammering out conclusions on controversial issues when consensus, both in the public and in the relevant disciplines, is not yet apparent"; and "a lightning rod for public concern—or viewed less charitably, dumping ground for an issue that is too difficult for the ordinary political process to handle" (Capron 1983, p. 9).Nearly every state has created a gubernatorial-level task force or commission on AIDS. The National Commission on AIDS was established under the Health Omnibus Program Extension (HOPE) Act of 1988, which was signed by President Reagan on November 4, 1988. The official charter of the commission was approved August 2, 1989 and its original two-year term was extended for a third year. The mission statement crafted by the commission to reflect its Congressional mandate reads: [End Page 339]The National Commission on Acquired Immune Deficiency Syndrome is an independent body of 15 members created to advise the President and Congress. The Commission seeks to build a broad public understanding on the magnitude, scope and urgency of the HIV/AIDS epidemic; provide and inspire leadership at all levels of both the public and private sectors; empower individuals and communities; and advocate for effective, cooperative and non-discriminatory resources required for prevention, comprehensive care, and the research necessary to halt the epidemic.As the mission statement implies, the National Commission on AIDS has viewed itself from the outset not only as a crucible for policy analysis, but also as a forum for those affected by HIV disease. In site visits and hearings the commissioners have met with hundreds of people living with HIV disease, and with caregivers on the front lines. This odyssey has taken the commission on visits to homeless shelters in New York City; to "shooting galleries" where intravenous drug users congregate in Seattle; to Native American communities in four states; to private homes in rural Georgia; and to hospitals, HIV antibody testing centers, drug treatment clinics, and hemophilia treatment centers throughout the nation. It quickly became clear during the commission's travels that HIV disease cannot be understood outside the context of the racism, homophobia, poverty and unemployment that provide the medium that fosters its spread. It also became apparent that issues of HIV prevention, care and treatment, and clinical research are inextricably intertwined and must be dealt with as such.Early InitiativesUnder the leadership of Chairperson June Osborn and Vice-chairperson David Rogers, the commission decided that the problems it saw in its first few meetings were too urgent to await a full-length annual report. Hence the commission entered the fray with a series of brief interim reports on particular aspects of AIDS. These reports enabled the commission to draw attention to urgent problems of limitations in access to health care and to underscore the plight of people with HIV disease who might otherwise garner little media attention, such as prisoners and drug users (National Commission... (shrink)

Almost every human disease has both a genetic and an environmental component. Even a classical inherited condition such as hemophilia can be influenced by external factors—in fact, most of the pathogenic effects of the mutation can be avoided by judicious injections of clotting factor, leading to a nearly normal life expectancy. For infectious diseases, often considered as essentially environmental, there are well-documented inherited differences in susceptibility, one of the most striking being the resistance to HIV infection of homozygous carriers (...) of the delta-32 mutation in the CCR5 gene (Dragic et al. 1996). Nevertheless, a number of conditions are “mostly genetic,” others “mostly environmental,” while many .. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal tissue from induced abortion (...) slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)

This chapter contains sections titled: Classical Genetics Modern Genetics How Genes Work DNA Function in Metabolism Differentiation Information, Structure and Function: Individuals and “Persons” Information and Individuals Personhood and “Me‐ness”.

The prelims comprise: Introduction Why is Testing Children a Moral Problem? A 37‐Nation Survey of Ethical Views A Clash of Autonomies: Parent and Child Survey Results When is a Child or Adolescent Ready to Know? Newborn Screening: The “Genetic Report Card” Prenatal Tests for Adult‐onset Disorders Commercialization Conclusion Acknowledgments.